Bioscience, Biotechnology, and Biochemistry
ISSN: 0916-8451 (Print) 1347-6947 (Online) Journal homepage: http://www.tandfonline.com/loi/tbbb20
Inhibition by Perilla Juice of Tumor Necrosis Factor Production Masatoshi Yamazaki, Hiroshi Ueda & Deji Du To cite this article: Masatoshi Yamazaki, Hiroshi Ueda & Deji Du (1992) Inhibition by Perilla Juice of Tumor Necrosis Factor Production, Bioscience, Biotechnology, and Biochemistry, 56:1, 152-152, DOI: 10.1271/bbb.56.152 To link to this article: http://dx.doi.org/10.1271/bbb.56.152
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Date: 06 May 2016, At: 00:37
Biosci. Biotech. Biochem., 56 (1), 152, 1992
Note
Inhibition by Perilla Juice of Tumor Necrosis Factor Production Masatoshi
YAMAZAKI,
Hiroshi
VEDA,
and Deji Du*
Downloaded by [93.115.95.216] at 00:37 06 May 2016
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-01, Japan Received July 5, 1991
Tumor necrosis factor (TNF), an endogenous cytokine with tumor necrosis activity secreted by macrophages, was recently recognized as an important host defense molecule that affects not only tumor cells, but many kind of normal cells. 1) However, prolonged exposure to TNF might contribute to the wasting of the host (cachexia) associated with many chronic disease states. 2 ) Moreover, acute overproduction of TNF in bacterial infection may induce septic shock leading to acute organ failure and death. 2 ) Therefore, inhibiting overproduction of TNF is a good step toward the suppression of acute and chronic inflammation. This work was undertaken to ascertain whether vegetable juice from Perilla leaf, which may be a new candidate for an antiinflammatory/immunosuppresive reagent, can inhibit the endogenous production of TNF in mice. Both red (Perilla frutescens (L.) Britton var. acuta Kudo) and green (Perilla frutescens (L.) Britton var. acuta Kudo forma viridis Makino) types of perilla (shiso in Japanese) were used in this study. Perilla leaves were homogenized with a mixer to obtain juices. Seven weeks old or more male C3H/He mice (6 mice/group) from Shizuoka Experimental Animal Farm (Shizuoka) were administered per os 500 Jig of muramyl dipeptide (MDP) (supplied by Daiichi Pharmaceutical Co.) and 3 hr later were given an intravenous injection of a bacterial reagent, OK-432 (3KE per mouse) which was supplied by Chugai Pharmaceutical Co. These mice produce much TNF in sera (about 1,000-3,000 units/ml). Perilla juice was administered per os into these TNF-overproducing mice 18 hr before and simultaneously with MDP-treatment. Serum TNF activity was measured by an in vitro cytotoxicity assay with L-929 cells as a target. 3) Units of activity were calculated as the dilution factor of the serum allowing survival of half the L-929 cells with a human recombinant TNF preparation as a standard. As shown in Table I, the TNF activities caused by MDP plus OK-432 without perilla juice were about 1,200-2,800 units/ml. TNF activity was significantly inhibited by per os administration of either the red or the green perilla juice (Expt. 1). Perilla juice was also effective with only one shot administration (Expt. II). Glucocorticoid is a powerful antiinflammatory Table I.
reagent and saibokuto, a Chinese medicine complex, is also widely used to treat inflammatory diseases in clinics. Experiment III shows that perilla juice has nearly the same inhibitory activity against TNF production as does saibokuto. This is the first report that selected vegetable juices inhibit the endogenous production of TNF when administered per os to normal animals. Both red and green perilla contain an active molecule(s) which can inhibit a host from releasing TNF. This molecule thus may suppress host defense systems as well as antiinflammatory drugs such as glucocoericoid or saibokuto. In fact, perilla juice is beneficial in the treatment of inflammatory skin disease (manuscript in preparation). The active molecule(s) described in our study, however, remains to be identified. We recently checked how vegetable juices affect TNF production in mice, to learn the effect of vegetables on host defense systems. Most vegetable juices could stimulate mice to produce TNF. 4 ) The inhibitory activity for TNF production was shown only by perilla and ginger juices among 18 vegetables tested (data not shown). In other words, vegetables may be divided into two groups in terms ofTNF production, enhancement and inhibition. These data suggest that plant foods have two opposite factors which enhance or inhibit host defense systems, corresponding to two groups of clinical drugs: immunopotentiaters and antiinflammatory reagents.
References 1) 2) 3)
4)
M. Yamazaki, Jpn. J. Inflammation, 10, 163-170 (1990). B. Sherry and A. Cerami, J. Cell Bioi., 107, 1269-1277 (1988). M. Satoh, H. Inagawa, H. Minagawa, T. Kajikawa, H. Oshima, S. Abe, M. Yamazaki, and D. Mizuno, J. Bioi. Res. Modij., 5,117123 (1986). M. Yamazaki, H. Ueda, K. Fukuda, M. Okamoto, and S. Yui, Biosci. Biotech. Biochem., 56, 149 (1992).
Inhibitory Effects of Perilla Juice on Tumor Necrosis Factor Production Sample administration Sample
Exp. I
Exp. II
Exp. III
18 hr before
ohr MDP-treatment
Red perilla (O.4ml/mouse) Green Perilla (0.4m1/mouse) None
+
+
+
+
Green perilla (O.4ml/mouse) Green perilla (O.4ml/mouse) Green perilla (0.4 ml/mouse) None
+
+
Glucocorticoid (0.25 mg/mouse) Saibokuto (50 mg/mouse) Green perilla (O.4ml/mouse) None
+ + +
+
+ +
+ +
TNF (Unit/ml)
Inhibition (%)
581±247 563±173 1,224±329
52.5 54.0 0
849±225 960± 137 1,500±443 2,868 ± 1,257
70.4 66.5 47.7 0
9±2 371 ±69 418±97 1,523 ±218
99.4 75.6 72.6 0
Abbreviations: TNF, tumor necrosis factor; MDP, muramy1 dipeptide. * Present address: Sichuan Institute of Chinese Materia Medica, Nan'an, Chongqing, Sichuan, China.
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